Monolayer pancreatic or islet cultures are used for the development, through cloning methods, of pure beta cell preparations which are used for more critical investigation of processes involved in insulin production. Such cultures are also tested for transplantation into diabetic animals. We will develop these cultures from rat, monkey, and human pancreas. Cultured cells (fibroblasts, arterial smooth muscle, skeletal muscle) from normal and diabetic donors of various ages are used to study insulin action, insulin binding, and cell growth. Comparisons of various metabolic functions (Sugar uptake, protein synthesis and content, nucleotide incorporation into RNA and DNA, DNA content) and cell growth rate are made between cells from young and old donors, normal and diabetic, to see if diabetic cells behave more like aged cells. Insulin resistance, if found, will be correlated, if possible, with insulin binding. Since alterations in collagen metabolism are probably closely related to the atherosclerotic, microangiopathic, and nephropathic consequences of diabetes, arterial specimens and cultures of fibroblasts, arterial smooth muscle cells, and renal glomeruli from normal and diabetic animals and humans are examined to determine early changes in collagen synthesis and maturation associated with the development of diabetic vessel disease.